PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-3 (3)
 

Clipboard (0)
None

Select a Filter Below

Journals
Authors
more »
Year of Publication
Document Types
author:("Zhu, bingo")
1.  CtIP is required for DNA damage-dependent induction of P21 
Cell Cycle  2013;13(1):90-95.
DNA endonuclease CtIP is involved in both DNA double-strand break (DSB) repair and transcriptional repression/activation. The cyclin-dependent kinase inhibitor P21, which is induced at transcription level in response to a variety of stresses, controls G1/S transition. In this report, we found that CtIP bound to the P21 promoter, and this binding was enhanced in response to DNA damage. Concomitantly, ectopic expression of CtIP increased P21 promoter activity, and this increment was enhanced upon camptothecin treatment. Conversely, DNA damage failed to induce P21 gene expression in CtIP-deficient cells. Taken together, our data demonstrate that CtIP is required for DNA damage-induced P21 induction.
doi:10.4161/cc.26810
PMCID: PMC3925741  PMID: 24196441
DNA endonuclease CtIP; DNA damage; P21
2.  Nampt is involved in DNA double-strand break repair 
Chinese Journal of Cancer  2012;31(8):392-398.
DNA double-strand break (DSB) is the most severe form of DNA damage, which is repaired mainly through high-fidelity homologous recombination (HR) or error-prone non-homologous end joining (NHEJ). Defects in the DNA damage response lead to genomic instability and ultimately predispose organs to cancer. Nicotinamide phosphoribosyltransferase (Nampt), which is involved in nicotinamide adenine dinucleotide metabolism, is overexpressed in a variety of tumors. In this report, we found that Nampt physically associated with CtIP and DNA-PKcs/Ku80, which are key factors in HR and NHEJ, respectively. Depletion of Nampt by small interfering RNA (siRNA) led to defective NHEJ-mediated DSB repair and enhanced HR-mediated repair. Furthermore, the inhibition of Nampt expression promoted proliferation of cancer cells and normal human fibroblasts and decreased β-galactosidase staining, indicating a delay in the onset of cellular senescence in normal human fibroblasts. Taken together, our results suggest that Nampt is a suppressor of HR-mediated DSB repair and an enhancer of NHEJ-mediated DSB repair, contributing to the acceleration of cellular senescence.
doi:10.5732/cjc.012.10089
PMCID: PMC3777511  PMID: 22704488
Nampt; DNA-PKcs/Ku80; CtIP; DNA repair; cellular senescence
3.  Protein phosphatase PP6 is required for homology-directed repair of DNA double-strand breaks 
Cell Cycle  2011;10(9):1411-1419.
DNA double-strand breaks (DSBs) are among the most lethal lesions associated with genome stability, which, when destabilized, predisposes organs to cancers. DSBs are primarily fixed either with little fidelity by non-homologous end joining (NHEJ) repair or with high fidelity by homology-directed repair (HDR). The phosphorylated form of H2AX on serine 139 (γ-H2AX) is a marker of DSBs. In this study, we explored if the protein phosphatase PP6 is involved in DSB repair by depletion of its expression in human cancer cell lines, and determined PP6 expression in human breast cancer tissues by immunohistochemistry staining. We found that bacterially produced PP6c (the catalytic subunit of PP6)-containing heterotrimeric combinations exhibit phosphatase activity against γ-H2AX in the in vitro phosphatase assays. Depletion of PP6c or PP6R2 led to persistent high levels of γ-H2AX after DNA damage and a defective HDR. Chromatin immunoprecipitation assays demonstrated that PP6c was recruited to the region adjacent to the DSB sites. Expression of PP6c, PP6R2 and PP6R3 in human breast tumors was significantly lower than those in benign breast diseases. Taken together, our results suggest that γ-H2AX is a physiological substrate of PP6 and PP6 is required for HDR and its expression may harbor a protective role during the development of breast cancer.
doi:10.4161/cc.10.9.15479
PMCID: PMC3117043  PMID: 21451261
protein phosphatase; PP6; γ-H2AX; DNA double-strand break; homology-directed repair

Results 1-3 (3)